Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes

Astrocytes express a complex repertoire of intracellular Ca²⁺ transients (events) that represent a major form of signaling within individual cells and in astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca²⁺ events appear more frequently in distal astrocytic processes and independently from each other. However, little is known about the mechanisms underlying such subcellular distribution of the Ca²⁺ events. Here, we identify the initiation points of the Ca²⁺ events within the territory of single astrocytes expressing genetically encoded Ca²⁺ indicator GCaMP2 in culture or in hippocampal slices. We found that most of the Ca²⁺ events start in an optimal range of thin distal processes. Our mathematical model demonstrated that a high surface-to-volume of the thin processes leads to increased amplitude of baseline Ca²⁺ fluctuations caused by a stochastic opening of Ca²⁺ channels in the plasma membrane. Suprathreshold fluctuations trigger Ca²⁺ -induced Ca²⁺ release from the Ca²⁺ stores by activating inositol 1,4,5-trisphosphate (IP₃ ) receptors. In agreement with the model prediction, the spontaneous Ca²⁺ events frequency depended on the extracellular Ca²⁺ concentration. Astrocytic depolarization by high extracellular K⁺ increased the frequency of the Ca²⁺ events through activation of voltage-gated Ca²⁺ channels in cultured astrocytes. Our results suggest that the morphological profile of the astrocytic processes is responsible for tuning of the Ca²⁺ events frequency. Therefore, structural plasticity of astrocytic processes can be directly translated into changes in astrocytic Ca²⁺ signaling. This may be important for both physiological and pathological astrocyte remodeling.